The multivalent presentation of carbohydrates on nanoparticles or polymers has been extensively studied. Due to the cluster glycoside effect, their intrinsic low affinity for lectins can is dramatically increased with as few as 2 or more glycans on the same scaffold. This increase in affinity is appealing as a route to develop materials which can target and bind pathogens (or their toxins) for diagnostics, treatment or prophylatics as well as basic biochemical research tools. Many strategies have been developed to present the glycans on polymers but the resulting affinity is often tested using limited techniques such as turbidity, and only against a single lectin. As such, whilst high affinities have been reported, there are comparatively less studies on the specificity and selectivity of glycopolymers, and methods to enable this.<br/>In this talk, I will describe the strategies we are using to develop glycopolymers which have increase selectivity, in particular towards bacterial toxins. This is accomplished by consideration of the binding mode of the native glycan targets, which are often branched and engage primary as well as allosteric binding sites. I will show the synthetic methods we use to both install the primary sugar of interest, along with secondary binding motifs. The binding of these polymers to lectins is assessed by both potency (inhibitory) assays as well as using bilayer interferometry, which enables high-throughput and quantitative evaluation of the binding process. The role of glycan heterogeneity in affinity will also be discussed as well as glycan density, highlighting that a 100 % functionalized polymer is not always needed. Using the above methods we have developed polymers with particular selectivity for the Cholera toxin compared to other galactose binding lectins.

Glycopolymers with selectivity as well as avidity through macromolecular enginnering

253rd National Meeting (2017)

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